Clinical outcomes of pomalidomide-based and daratumumab-based therapies in patients with relapsed/refractory multiple myeloma: A real-world cohort study in China.

BACKGROUND: Comparative investigations evaluating the efficacy of pomalidomide-based (Pom-based) versus daratumumab-based (Dara-based) therapies in patients with relapsed/refractory multiple myeloma (RRMM) remain scarce, both in randomized controlled trials and real-world studies. METHODS: This retrospective cohort study included 140 RRMM patients treated with Pom-based or Dara-based or a combination of pomalidomide and daratumumab (DPd) regimens in a Chinese tertiary hospital between December 2018 and July 2023. RESULTS: The overall response rates (ORR) for Pom-based (n = 48), Dara-based (n = 68), and DPd (n = 24) groups were 57.8%, 84.6%, and 75.0%, respectively (p = 0.007). At data cutoff on August 1, 2023, the median progression-free survival (PFS) was 5.7 months (95% CI: 5.0-6.5) for the Pom-based group, 10.5 months (5.2-15.8) for the Dara-based group, and 6.7 months (4.0-9.3) for the DPd group (p = 0.056). Multivariate analysis identified treatment regimens (Dara-based vs. Pom-based, DPd vs. Pom-based) and Eastern Cooperative Oncology Group performance status (ECOG PS) as independent prognostic factors for PFS. In the subgroups of patients aged >65 years, with ECOG PS ≥2, lines of therapy ≥2, extramedullary disease or double-refractory disease (refractory to both lenalidomide and proteasome inhibitors), the superiority of Dara-based regimens over Pom-based regimens was not evident. A higher incidence of infections was observed in patients receiving Dara-based and DPd regimens (Pom-based 39.6% vs. Dara-based 64.7% vs. DPd 70.8%, p = 0.009). CONCLUSIONS: In real-world settings, Pom-based, Dara-based, and DPd therapies exhibited favorable efficacy in patients with RRMM. Dara-based therapy yielded superior clinical response and PFS compared to Pom-based therapy.

A Quantitative Detection Algorithm for Multi-Test Line Lateral Flow Immunoassay Applied in Smartphones.

The traditional lateral flow immunoassay (LFIA) detection method suffers from issues such as unstable detection results and low quantitative accuracy. In this study, we propose a novel multi-test line lateral flow immunoassay quantitative detection method using smartphone-based SAA immunoassay strips. Following the utilization of image processing techniques to extract and analyze the pigments on the immunoassay strips, quantitative analysis of the detection results was conducted. Experimental setups with controlled lighting conditions in a dark box were designed to capture samples using smartphones with different specifications for analysis. The algorithm's sensitivity and robustness were validated by introducing noise to the samples, and the detection performance on immunoassay strips using different algorithms was determined. The experimental results demonstrate that the proposed lateral flow immunoassay quantitative detection method based on image processing techniques achieves an accuracy rate of 94.23% on 260 samples, which is comparable to the traditional methods but with higher stability and lower algorithm complexity.

Pathogenicity of Plesiomonas shigelloides and Citrobacter freundii isolated from the endangered Chinese sturgeon (Acipenser sinensis).

Chinese sturgeon (Acipenser sinensis) is an indigenous species of China and is listed as a critically endangered species. Recently, second filial generations of Chinese sturgeon in the Yangtze River Fisheries Research Institute suffered from a severe disease. In this study, two kinds of pathogenic bacteria were isolated from diseased sturgeon and identified as Plesiomonas shigelloides and Citrobacter freundii, based on 16S rDNA gene sequence alignment analysis. Antimicrobial susceptibility testing showed that P. shigelloides was resistant to ampicillin, penicillin, midecamycin, oxacillin, and clindamycin; and sensitive to tocefatriaxone, piperacillin, cefoperazone, cefazolin, and ciprofloxacin. C. freundii was resistant to ampicillin, penicillin, midecamycin, oxacillin, and clindamycin; and sensitive to chloramphenicol, cefuroxime, norfloxacin, ciprofloxacin, and ceftazidime. The median lethal dose (LD50) values of P. shigelloides and C. freundii were 4.50 × 103 colony forming units (CFU)/g and 3.20 × 103 CFU/g, respectively. Clinical symptoms of challenged sturgeons were the same as those of naturally infected sturgeons. Histopathological examination disclosed severe damage in the viscera of P. shigelloides and C. freundii-infected sturgeons. This is the first report suggesting that P. shigelloides infection is associated with mortality of Chinese sturgeon. The results of this study revealed the pathogenesis and severe pathogenicity of P. shigelloides and C. freundii in cultured Chinese sturgeon, and offer insights into the prevention and treatment of bacterial infection caused by P. shigelloides and C. freundii in cultured sturgeons.

Interspecific competition between Microcystis aeruginosa and Chlamydomonas microsphaera stressed by tetracyclines.

The extensive use of tetracyclines in human and veterinary medicine causes contamination in the environment that could contribute to the spread of antibiotic-resistant bacteria or competition between species of phytoplankton. In this study, Microcystis aeruginosa (a bloom-forming cyanobacterium) and Chlamydomonas microsphaera (common green alga) were selected to test the effects of different concentrations of tetracyclines (tetracycline and oxytetracycline) in monoculture and co-culture. The results showed that compared with monoculture, the cell growth of C. microsphaera decreased significantly in co-culture treated with different concentrations of tetracycline and oxytetracycline. The ratios of inhibition of M. aeruginosa exposed to 0.1, 2, and 10 mg L-1 of tetracycline varied between 17.7 and 31.37% in co-culture compared with monoculture, while the cell growth of M. aeruginosa was enhanced by treatment with 0.1, 2, and 7.25 mg L-1 of oxytetracycline in co-culture. However, the cell growth of C. microsphaera was significantly inhibited by all the treatments in co-culture. With the treatment of tetracycline, the specific growth rate of M. aeruginosa was 0.36 to 0.31 day-1 in monoculture and co-culture, while that of C. microsphaera ranged from 0.38 to 0.26 day-1 in monoculture, and it decreased from 0.25 day-1 (0 mg L-1) to 0.08 day-1 (10 mg L-1) in co-culture. With the treatment of oxytetracycline, the specific growth rate of M. aeruginosa was stimulated in co-culture, while that of C. microsphaera was significantly inhibited in co-culture compared with monoculture. Therefore, although M. aeruginosa significantly inhibited C. microsphaera in co-culture with the tetracycline-free treatment, the competitive advantage of M. aeruginosa expanded following the addition of low or high concentrations of tetracyclines.

Left Atrial Function Predicts Outcome in Dilated Cardiomyopathy: Fast Long-Axis Strain Analysis Derived from MRI.

Background There is increasing recognition that left atrial (LA) function is prognostically important in cardiovascular disease. LA strain is a sensitive parameter to describe complex LA phasic function. However, the prognostic value of LA strain in participants with idiopathic dilated cardiomyopathy (DCM) remains unclear. Purpose To evaluate the prognostic value of LA strain derived from cardiac MRI in study participants with idiopathic DCM. Materials and Methods Participants with idiopathic DCM who underwent cardiac MRI between June 2012 and November 2018 were prospectively enrolled. The fast long-axis strain MRI method was performed to assess LA strain. The primary end point was all-cause mortality and heart transplant, and the secondary end point was a combination of primary end point, heart failure readmission, and aborted sudden cardiac death. Cox regression analyses and Kaplan-Meier survival analysis were performed to identify the association between variables and outcomes. Results There were 497 participants (mean age, 47 years ± 14 [standard deviation]; 357 men) evaluated. During a median follow-up of 36 months (interquartile range, 26-54 months), 113 participants reached primary end points and 203 participants reached secondary end points. LA reservoir, conduit and booster strain, and strain rate were lower in participants with primary end points (P < .001). In multivariable Cox regression analysis, LA reservoir strain and conduit strain were independent predictors for primary end point (hazard ratio [HR] per 1% increase, 0.95 [95% CI: 0.91, 0.99; P = .008] and 0.92 [95% CI: 0.87, 0.98; P = .010], respectively) and secondary end points (HR per 1% increase, 0.95 [95% CI: 0.93, 0.97; P < .001] and 0.93 [95% CI: 0.89, 0.97; P < .001], respectively). In addition, LA reservoir strain and conduit strain added incremental prognostic value to clinical risk factors and late gadolinium enhancement presence (all, P < .05). Conclusion Left atrial reservoir and conduit strain, derived from cardiac MRI by using the fast long-axis method, were independent predictors of adverse clinical outcomes in idiopathic dilated cardiomyopathy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Ambale-Venkatesh in this issue.

Low-pressure UV-initiated synthesis of cationic starch-based flocculant with high flocculation performance.

A kind of starch-based flocculant (starch-graft-poly[(2-methacryloyloxyethyl) trimethyl ammonium chloride], denoted St-g-PDMC-LPUV) has been synthesized by low-pressure ultraviolet initiation and was employed to remove humic acid (HA) for water purification. The physicochemical characteristics of starch and St-g-PDMC-LPUV were characterized by FT-IR, 1H NMR, XRD, TGA, SEM and BET to confirmed the successful grafting DMC onto starch. Effects of flocculant dosage, pH, the adding amount of Fe3O4, initial HA concentration and stirring speed were investigated systematically. The prepared St-g-PDMC-LPUV flocculant with non-toxic, biodegradability and environmental friendliness exhibited effective performance for removing HA from water in a wide pH range (5-10). The flocculation mechanism was attributed to the effective collision between function groups of the St-g-PDMC-LPUV flocculant and HA by charge neutralization, adsorption, bridging and patching.

Biopolymer-based flocculants: a review of recent technologies.

Biopolymer-based flocculants have become a potential substitute for inorganic coagulants and synthetic organic flocculants due to their wide natural reserves, environmental friendliness, easy natural degradation, and high material safety. In recent years, with more and more attention to clean technologies, a lot of researches on the modification and application of biopolymer-based flocculants have been carried out. The present paper reviews the latest important information about the base materials of biopolymer-based flocculants, including chitosan, starch, cellulose, and lignin etc. This review also highlights the various modification methods of these base materials according to reaction types in detail. Via the recent researches, the flocculation mechanisms of biopolymer-based flocculants, such as adsorption, bridging, charge neutralization, net trapping, and sweeping, as well as, some other special mechanisms are comprehensively summarized. This paper also focuses on the water treatment conditions, the removal efficiency, and advantages of biopolymer-based flocculants in applications. Further, this review sheds light on the future perspectives of biopolymer-based flocculants, which may make progress in the sources of base materials, modification processes, multi-function, and deepening application researches. We believe that this review can guide the further researches and developments of biopolymer-based flocculants in the future, to develop them with a higher efficiency, a lower cost, more safety, and multi-function for more diversified applications. Graphical abstract.

Myocardial Tissue Reverse Remodeling After Guideline-Directed Medical Therapy in Idiopathic Dilated Cardiomyopathy.

BACKGROUND: The prognosis of patients with idiopathic dilated cardiomyopathy (DCM) has improved remarkably in recent decades with guideline-directed medical therapy. Left ventricular (LV) reverse remodeling (LVRR) is one of the major therapeutic goals. Whether myocardial fibrosis or inflammation would reverse associated with LVRR remains unknown. METHODS: A total of 157 prospectively enrolled patients with DCM underwent baseline and follow-up cardiovascular magnetic resonance examinations with a median interval of 13.7 months (interquartile range, 12.2-18.5 months). LVRR was defined as an absolute increase in LV ejection fraction of >10% to the final value of ≥35% and a relative decrease in LV end-diastolic volume of >10%. Statistical analyses were performed using paired t test and student t test, logistic regression analysis, and linear regression analysis. RESULTS: Forty-eight (31%) patients reached LVRR. At baseline, younger age, worse New York Heart Association class, new-onset heart failure, lower LV ejection fraction, absence of late gadolinium enhancement, lower myocardial T2, and extracellular volume were significant predictors of LVRR. During the follow-up, patients with and without LVRR both showed a significant decrease of myocardial native T1 (LVRR: [baseline] 1303.0±43.6 ms; [follow-up] 1244.7±51.8 ms; without LVRR: [baseline] 1308.5±80.5 ms; [follow-up] 1287.6±74.9 ms, both P<0.001), matrix and cellular volumes while no significant difference was observed in T2 or extracellular volume values after treatment. CONCLUSIONS: In patients with idiopathic DCM, the absence of late gadolinium enhancement, lower T2, and extracellular volume values at baseline are significant predictors of LVRR. The myocardial T1, matrix, and cell volume decrease significantly in patients with LVRR after guideline-directed medical therapy. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: ChiCTR1800017058.

Association between Health-Related Physical Fitness and Risk of Dyslipidemia in University Staff: A Cross-Sectional Study and a ROC Curve Analysis.

BACKGROUND: This study aimed to assess the relationship between dyslipidemia (DL) risk and health-related physical fitness (HPF) and evaluated the prognostic value of HPF for risk of DL. METHODS: A total of 776 university staff members were recruited, of which 407 were females, and 369 males. Blood samples and HPF tests were collected from all participants after 12 h fasting. RESULTS: The prevalence of DL was 41.77% and 51.49% in female and male university staff members, respectively, and there was no significant difference between genders (χ2 = 2.687, p = 0.101). According to the logistic regression analysis, age, male sex, GLU, hypertension, BMI, BF, WHtR, and LAP were significant risk factors for DL (p < 0.05), VCI and, SAR were significant protective factors for DL (p < 0.05), and SMI, GS, and VG were not significantly associated with the risk of DL. The area under the receiver-operating characteristic (ROC) curve (AUC) analysis indicated that, LAP (AUC: 0.730, 95CI%: 0.697-0.762), WHtR (AUC: 0.626, 95CI%: 0.590-0.660), and BMI (AUC: 0.599, 95CI%: 0.563-0.634) are valid predictors of DL, and LAP and WHtR perform better than BMI (Z = 8.074, p < 0.001) in predicting DL in male and female university staff members. CONCLUSION: The risk of DL is significantly related to body composition, cardiorespiratory fitness, and flexibility. LAP and WHtR perform better than BMI in predicting risk of DL in male and female university staff members.

The phenotypic characteristic observed by cardiac magnetic resonance in a PLN-R14del family.

Phospholamban (PLN) is an important regulator for sarcoendoplasmic reticulum (SR) calcium transport ATPase (SERCA), which uptakes Ca2+ to SR during the diastolic phase of cardiomyocytes to maintain intracellular calcium homeostasis. Mutations on PLN result in intracellular calcium disorder, myocardial contraction defect, and eventually heart failure and/or malignant ventricular arrhythmia. Since 2003, several kinds of PLN mutations have been identified in familial dilated cardiomyopathy (DCM) patients, illustrating a few clinical characteristics that differs from classical DCM patients. Herein, we report a large PLN-R14del family with typical clinical characteristics reported including relatively late-onset clinical symptoms, low-voltage in ECG, as well as frequent ventricular arrythmias. Moreover, members underwent cardiac magnetic resonance (CMR) examination showed a strikingly similar pattern of late gadolinium enhancement (LGE)-Sub-epicardial involvement in the left ventricular (LV) lateral wall with or without linear mid-wall enhancement in the interventricular septum. The former one can also present in younger PLN-R14del carriers despite completely normal LV structure and function. Meanwhile, T1 mapping also found significantly increased extracellular volume (ECV) in PLN-R14del carriers. These findings highlight the special role of CMR to phenotyping PLN-induced cardiomyopathy patients and distinguish them from other types of cardiomyopathy.

Copper foam in situ loaded with precious metal nanoparticles as transmission SEIRAS substrate for rapid detection of dithiocarbamate pesticides.

A transmission surface-enhanced infrared absorption spectroscopy (SEIRAS) substrate based on copper foam (CF) was developed for the rapid detection of dithiocarbamate (DTC) pesticides. The transmission SEIRAS substrate was prepared by immersing CF in a mixed solution of a precious metal solution and a polyvinyl pyrrolidone (PVP) solution. Then CF could be in situ loaded with precious metal nanoparticles (MNPs) by PVP-modified displacement reaction in seconds. PVP could be helpful for the uniform distribution of MNPs. Experimental parameters were evaluated with 11-mercaptoundecanoic acid (MUA) as a probe molecule, including the concentration of the precious metal solution, the amount of PVP, and the reaction time. Taking CF loaded with gold nanoparticles (Au NPs-CF) as an example, the signal intensity of DTC pesticide (Ziram) could be enhanced by two orders of magnitude, and the R2 of the calibration curve was 0.999. In addition, the Pt NPs-CF substrate was applied to the rapid detection of other DTC pesticides (Ferbam). In summary, we have developed a new method to prepare the transmission SEIRAS substrate and apply it to the rapid detection of DTC pesticides in liquid.

Observation and analysis of VOCs in nine prefecture-level cities of Sichuan Province, China.

The observation and analysis of volatile organic compounds (VOCs) were conducted during January 2018 in nine prefecture-level cities of Sichuan, China, covering the period of heavily polluted weather. Air samples collected in nine prefecture-level cities were analyzed using a preconcentration method coupled with GC-MS/FID. The characteristics and ozone generation potential (OFP) of VOCs were analyzed. The relationship between air quality index (AQI) and VOCs and gross domestic product (GDP) and VOCs were also discussed, respectively. The results show that the characteristics of VOCs in cities are highly related to their industrial structure and GDP. Generally, areas with high AQI values are accompanied by high VOC concentrations. Alkanes and halocarbons were the most abundant VOCs in the atmospheric environment in the nine prefecture-level cities, accounting for 24.5~61.6% and 15.6~23.6% of total VOC concentration, respectively. The MIR method was used to analyze the OFP, and olefins contributed the most to ozone formation. Among the nine cities located in Sichuan, Dazhou was found to be the city with the highest OFP value (1191.49 µg/m3).

The Effects of a Trace Amount of Manganese and the Homogenization on the Recrystallization of Al-7Mg-0.15Ti Alloys.

The aim of this study is to explore the effects of Manganese addition and homogenization treatment on the microstructures and mechanical properties of the Al-7Mg-0.15Ti (B535.0) alloy. The optical microscopy, electrical conductivity measurements, transmission electron microscopy, scanning electron microscopy (SEM + EBSD), as well as Rockwell hardness and tensile tests, were exploited for this purpose. The main objectives are to refine the grain size, inhibit grain growth in the annealed state, and enhance the mechanical strength of the alloy. The results show that the addition of manganese to the Al-7Mg-0.15Ti alloys refined the as-cast and recrystallized grains of the alloys. During the homogenization process, Al4Mn high-temperature stable dispersoids were precipitated in the aluminum matrix. After annealing, the Al4Mn particles blocked the movement of grain boundaries during the growth of the recrystallized grains and inhibited grain growth. Consequently, the annealed alloys showed grain refinement and dispersion strengthening. The Al4Mn dispersoids of the alloys with manganese added were smaller and denser after a two-stage homogenization process compared to those that underwent a one-stage homogenization process. By contrast, for the alloys without the addition of manganese, the recrystallized grains showed normal growth after annealing, and different homogenization processes had no significantly different effects.

Identification of gene variants in 130 Han Chinese patients with hypospadias by targeted next-generation sequencing.

BACKGROUND: Hypospadias is a common congenital malformation of male external genitalia, which mainly manifests as an abnormal urethral opening on the ventral side of the penis. The etiology and clinical phenotype of hypospadias is highly heterogeneous, and its clinical diagnosis is challenging. Currently, over 70% of patients have an unknown etiology. Here, we performed a targeted analysis of gene mutations in 130 patients with hypospadias of unknown etiology to find the precise genetic cause. METHODS: We developed a targeted next-generation sequencing (NGS) panel, encompassing the exon coding regions of 105 genes involved in external genitalia and urogenital tract development and performed sequencing analysis on 130 children with hypospadias of unknown etiology. RESULTS: In total, 25 patients with hypospadias (19.2%) were found to have 20 mutations among the nine genes involved in external genitalia and urogenital tract development, including 16 reported and four novel mutation sites. Twenty-two patients (16.9%) had diagnostic variants. Multiple genetic mutations were identified in three of the 25 patients. Hypospadias combined with micropenis was the most common phenotype (68%) in 25 patients. CONCLUSIONS: Higher frequency mutations were identified in SRD5A2 (52%) and AR (24%) in our patient cohort. Middle or posterior hypospadias with micropenis may be significant indicators of genetic variations. Polygenic inheritance may be a rare genetic cause of hypospadias.

Co-delivery of VEGF and bFGF via a PLGA nanoparticle-modified BAM for effective contracture inhibition of regenerated bladder tissue in rabbits.

Graft contracture is a common problem associated with the regeneration processes of tissue-engineered bladders. Currently, most strategies used for incorporating bioactive molecules into biomaterial designs do not work during all phases of tissue regeneration. In this study, we used a growth factor-PLGA nanoparticle thermo-sensitive gel system (i.e., BAM with incorporated VEGF and bFGF-loaded PLGA nanoparticles and mixed with a hydrophilic gel) to promote bladder tissue regeneration in a rabbit model. At 4 and 12 weeks after surgery, contracture rate assessment and histological examination were conducted to evaluate bladder tissue regeneration. The results indicated that the functional composite scaffold continuously and effectively released VEGF and bFGF and promoted bladder reconstruction with a significant decrease in graft contracture. In addition, the number and arrangement of regenerated urothelial cells and smooth muscle cells as well as microvascular density and maturity were improved in the VEGF/bFGF nanoparticle group compared with the single factor VEGF or bFGF nanoparticle group and BAM alone. The nanoparticle thermo-sensitive gel system, which exhibited favourable performance, may effectively inhibit graft contracture and promote bladder tissue regeneration in rabbits.

VEGF-Loaded Nanoparticle-Modified BAMAs Enhance Angiogenesis and Inhibit Graft Shrinkage in Tissue-Engineered Bladder.

Insufficient angiogenesis is a common problem in bladder tissue engineering and is believed to be a major factor responsible for graft shrinkage. In this study, we investigated the use of bladder acellular matrix allografts (BAMAs) modified with vascular endothelial growth factor (VEGF)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for the long-term sustained release of VEGF to enhance blood supply and inhibit graft shrinkage in a rabbit model of bladder reconstruction. Rabbits underwent partial bladder cystectomy using a 2 × 3 cm BAMA modified with VEGF-loaded PLGA NPs in the experimental group, while no modification was used in the control. Histology and immunohistochemical analyses showed that urothelium, smooth muscle fibers and blood vessels were formed in both groups at 4 and 12 weeks postoperatively. The microvessel density in the experiment group was significantly higher than that in control and the contracture rate declined to 27%. In vitro functional experiments indicated that the characteristics of regenerated bladders were similar to native bladders. The VEGF release from BAMA in vivo was almost 83% within 3 months. Our data demonstrated the effectiveness of VEGF-loaded PLGA NPs-modified BAMAs to enhance neovascularization and solve the problems of insufficient angiogenesis and graft shrinkage associated with bladder tissue engineering.